Ligand-targeting has been a major advancement in nanoparticle (NP) mediated drug delivery, achieving high local concentration and low systemic exposure, reducing drug toxicity while maintaining optimal dose delivery to target cells. Proof of concept was established for this strategy with antibodies and homing peptides, which bind adhesion receptors that are over expressed by tumor vasculature, including integrins, and HER-2, and folate cell surface receptors on tumor cells. Concerns associated with ligand-targeting include receptor saturation, low receptor-ligand affinity, limited tissue penetration and genetic heterogeneity of solid tumors. Legumain is an asparaginyl endopeptidase that is overexpressed by a variety of tumor cells. Consequently, legumain provides a convenient target for directing therapeutic agents to tumor cells. The compositions and methods of the present described herein address the concerns associated with ligand-targeting, while providing effective means for tumor-specific drug delivery.